14-75702965-C-T

Variant names:

• chr14-75702965-C-T
• rs10483872
• NM_015072.5:c.585+3695C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015072.5(TTLL5):​c.585+3695C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0858 in 152,234 control chromosomes in the GnomAD database, including 680 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.086 (680 hom., cov: 32)
• Consequence: TTLL5 NM_015072.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.747
• Publications: 7 publications found

Genes affected

TTLL5 (HGNC:19963): (tubulin tyrosine ligase like 5) This gene encodes a member of the tubulin tyrosine ligase like protein family. This protein interacts with two glucocorticoid receptor coactivators, transcriptional intermediary factor 2 and steroid receptor coactivator 1. This protein may function as a coregulator of glucocorticoid receptor mediated gene induction and repression. This protein may also function as an alpha tubulin polyglutamylase.[provided by RefSeq, Feb 2010]

TTLL5 Gene-Disease associations (from GenCC):

• cone-rod dystrophy 19

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• TTLL5-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015072.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTLL5	NM_015072.5	MANE Select	c.585+3695C>T		intron	N/A	NP_055887.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTLL5	ENST00000298832.14	TSL:1 MANE Select	c.585+3695C>T		intron	N/A	ENSP00000298832.9	Q6EMB2-1
	TTLL5	ENST00000557636.5	TSL:1	c.585+3695C>T		intron	N/A	ENSP00000450713.1	G3V2J9
	TTLL5	ENST00000882579.1		c.585+3695C>T		intron	N/A	ENSP00000552638.1

Frequencies

GnomAD3 genomes AF: 0.0858 AC: 13058 AN: 152116 Hom.: 679 Cov.: 32

Gnomad AFR AF: 0.0455

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0853

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.0642

Gnomad SAS AF: 0.0592

Gnomad FIN AF: 0.0660

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.0959

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0858 AC: 13059 AN: 152234 Hom.: 680 Cov.: 32 AF XY: 0.0832 AC XY: 6194 AN XY: 74432

African (AFR) AF: 0.0455 AC: 1890 AN: 41564

American (AMR) AF: 0.0854 AC: 1305 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 466 AN: 3470

East Asian (EAS) AF: 0.0641 AC: 332 AN: 5176

South Asian (SAS) AF: 0.0585 AC: 282 AN: 4824

European-Finnish (FIN) AF: 0.0660 AC: 700 AN: 10600

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7778 AN: 67998

Other (OTH) AF: 0.0954 AC: 201 AN: 2108

Alfa AF: 0.105 Hom.: 1519

Bravo AF: 0.0870

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.59
PhyloP100		0.75
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10483872; hg19: chr14-76169308;